Here’s an interesting chart (although, portraying pandemics as spiky spheres is a bad choice — people are not good at visualizing relative volumes, and putting those volumes in a perspective that reduces the size of older one is a terrible idea) showing various afflictions on the human species over time.
The Black Death was the big one, but look at HIV — it’s amazing how our culture diminished the significance of that one, pretending it wasn’t happening even as its victims were dying in hospitals, and as prominent figures fell to it.
Smallpox coulda been a contender for the biggest plague of them all, but humans invented something that stopped it in its tracks: vaccination. If only people recognized the importance of that today…